Neuronal electric activity is the major factor that shapes the appropriate synaptic connectivity in a developing nervous system and regulates synaptic efficacy during learning in adult animals. Growing neurites and mature synaptic terminals share many common features and are responsible for such developmental and physiological plasticity. This project examines the functional and morphological plasticity of nerve terminals and the influence of electric activity on neuronal development by using a combination of genetic, physiological and anatomical techniques. The Drosophila mutants dnc, rut, and ala, each affects a specific step in the cAMP and Ca-calmodulin second messenger systems, show diminished learning ability. In addition, several mutants with defective K+ and Na+ channels will be used to generate different patterns of spontaneous activity. Studies of these mutants and their double mutant combinations allow us to determine how nerve activity and second messenger systems interact to regulate neurite outgrowth and synaptic plasticity. We have developed a culture system of "giant" Drosophila neurons derived from cell division-arrested neuroblasts. These neurons display a variety of branching patterns and electric activity seen in normal neurons but their increased size greatly facilitates the physiological and cell biological investigations of Drosophila mutants. In situ studies of terminal aborization and synaptic transmission will be performed on larval neuromuscular junctions. These motor axonal terminals exhibit activity-dependent plasticity and offer a unique opportunity for physiological and morphological analysis at the level of individual synaptic boutons. Results from the proposed studies will provide useful information about the cellular mechanisms underlying learning and memory behavior and the regulatory mechanisms common to functional and developmental plasticity in the nervous system.